Effects of multi-intravenous transplantation of human cord blood mononuclear cells on inflammatory responses after myocardial infarction in rabbits

Abstract

Objective To investigate the effects of multi-intravenous transplantation of human cord blood mononuclear cells(HUMNCs)on inflammatory responses and interleukin-6(IL-6),IL-10 after myocardial infarction in rabbits.Methods Totally 45 Chinese rabbits were randomly divided into three groups:multi-transplantation group,single cell transplantation group,control group.The rabbits in control group(n=15),which had undergone ligation of the left anterior coronary artery(LAD),were intravenously injected with normal saline 7,9,11,13 days after the operation.The rabbits in single transplantation group(n=15)were intravenously injected with 3×106 HUMNCs labeled with bromodexyuridine(BrdU)at 7th day after the operation,and normal saline at 9th,11th,13th day post-operation.The rabbits in multiple transplantation group(n=15)were intravenously injected with 3×106 HUMNCs labeled with BrdU at 7th,9th,11th,and 13th day after the operation.In addition,10 Chinese rabbits served as the sham operation group,receiving the operation without ligation of the LAD.Cardiac functions were examined by echocardiography,and pathohistological changes of the myocardia were observed under the microscopy.The BrdU positive cells and the expression of IL-6 and IL-10 in the myocardia were examined by immunohistochemical method and ELISA.Results(1)Compared to control group,transplantation of HCBMCs improved left ventricular ejection fraction(LVEF)(P<0.05),while LVEF was improved more significantly in multi-transplantation group than in single-transplantation group(P<0.05);(2)BrdU positive cells were found in the peri-myocardial infarction area in both transplantation groups.Moreover,compared to single transplantation group,the number of BrdU positive cells was increased,and that of inflammatory cells was decreased in multi-transplantation group(P<0.05);(3)Compared to control group,the expression levels of IL-6 were decreased,andthose of IL-10 increased in both transplantation groups.Compared to single transplantation group,the expression levels of IL-6 were further decreased (P<0.05),and those of IL-10 further increased in multi-transplantation group (P<0.05).Conclusion The regulation of the inflammatory factors IL-6 and IL-10 in the myocardia is one of the possible mechanisms responsible for acute myocardial infarction treated by intravenous administration of HCBMCs.The multiple intravenous HCBMCs transplantation for myocardial infarction was superior to single intravenous transplantation in improving cardiac function and inhibiting inflammatory responses in the infarct area. Key words: Monocytes; Transplantation; Acute myocardial infarction